Serial monitoring of divalent cation levels and markers of bone remodeling before, during, and after platelet- and leukocytapheresis procedures revealed that apheresis induces an acute and dramatic increase in parathyroid hormone, accompanied by a reduction in osteocalcin, and an increase in c-telopeptide and vitamin D levels. Some of these changes persisted for as long as 14 days after apheresis, with the degree of change more closely elated to the rate at which citrate was administered rather than the total amount of citrate given. Bone density assessments showed that NIH plateletpheresis donors had significantly higher bone density measurements than control whole blood donors. Plateletpheresis donor also had higher bone density scores than reference population standards provided by the DEXA-instrument manufacturer. A less markedly positive effect on bone density was observed in NIH leukapheresis donors, who also had bone density scores higher than those of the reference and control non-apheresis populations. These findings of an increased bone density in NIH platelet- and leukapheresis donors are consistent with the anabolic effects of parathyroid hormone on bone when it is released in a pulsatile rather than a tonic fashion, and may be related to the increased levels of osteoprotegerin that were seen in NIH platelet donors. Osteoprotegerin synthesis appears to be induced by repeated apheresis donations performed on an every 4 week cycle; this molecule blocks the activation of osteoclast cells which can induce bone breakdown. The degree of this effect is likely to be impacted by the frequency and rapidity (blood flow rate or citrate administration rate) of apheresis procedures. Studies are continuing to evaluate the impact of prophylactic intravenous calcium supplementation during apheresis on bone density markers.